This project is concerned with investigation of the control of placental progesterone synthesis via in vitro studies of various substances endogenous to the placenta which affect delta 5 beta 3-hydroxy-steroid dehydrogenase. 1) Endogenous steroids: 20 alpha hydroxy-4-pregnen-3-one and cortisone inhibit placental delta 5 3 beta HSD in a number of species (man, rhesus, cow, goat, rat). Studies will be extended to further species to test the prevalence of this phenomenon. 2) In all the above species, delta 5 3 beta HSD shows an increased specific activity on dilution, indicating another endogenous inhibitor. The nature and mode of action of this inhibitor, which appears in human placenta in greater amounts after delivery than before, will be investigated. So far, indications are that it is a small (less than 12,000 MW) unstable molecule, non-protein, and not a prostaglandin. 3) Recently, evidence has been obtained for the existence of an endogenous activator in placenta. This substance which is relatively stable and is dialysable, will be investigated for its nature and mode of action.